20 April 2007
US FDA
Approves Initial Human Vaccine against H5N1 (Clade 1) Avian Influenza Virus
for the Strategic National Stockpile (SNS)
This week the Food
And Drug Administration (FDA) announced approval of the first human vaccine to
prevent infection with the H5N1 avian influenza virus. This vaccine is made by sanofi pasteur,
Inc., and will be manufactured in Swiftwater, Pennsylvania. It will not be
available commercially. Instead, it will be purchased by the US government for
storage in the Strategic National Stockpile (SNS) for potential future use for
prioritized recipients.
In a press release on
April 17, the FDA Commissioner, Dr. Andrew C. von Eschenbach stated: “The
threat of an influenza pandemic is, at present, one of the most significant
public health issues our nation and world faces. The approval of this vaccine
is an important step forward in our protection against a pandemic.” www.fda.gov/bbs/topics/NEWS/2007/NEW01611.html
Although generally
well tolerated in terms of side effects (e.g., pain at the injection site,
headache, muscle pain, and “a general ill feeling”, according to the FDA) by
the approximately 400 healthy adult volunteers, the immune responses induced by
the vaccine were less than optimal. For example, only 45% of the vaccines who
received the highest dose of the vaccine (90 micrograms of H5N1 antigen),
intramuscularly on two occasions one month apart, produced antibody levels
(titers) considered to be protective against human influenza infection. Thus,
this vaccine is a starting point from which to compare future H5N1 vaccines.
This initial H5N1
human vaccine does not include any vaccine adjuvant, such as alum or
MF-59. Also of potential importance, it uses a Clade 1 form
of the H5N1 virus that was prevalent during the early outbreaks in 2003-2004 in
Vietnam and Thailand. More recent outbreaks in 2005-2006 in other nations have
involved predominantly a Clade 2 form of the virus (and subclades of Clade 2,
according to the WHO H5N1 avian flu website postings). Clade 2-based H5N1 vaccines have already
begun to be developed, but none are published yet in the medical literature.
Writing on the
vaccine’s approval in the New York Times on April 18, 2007 (page A21), Andrew
Pollack quoted Norman Baylor, head of the vaccine office at the FDA as
describing this vaccine as an “interim measure”, and that future H5N1 vaccines
would hopefully have higher than 45% efficacy, and ideally only require one
shot and less H5N1 antigen.
The vaccine’s
efficacy is estimated based on the antibody levels produced by the immune
response after two shots of the vaccine. No human volunteers were exposed to
the actual H5N1 virus after receiving either the vaccine or the placebo. It
would be considered unethical to expose human volunteers to a virus that
currently has approximately a 60% mortality rate based on the nearly 300
persons with laboratory-confirmed H5N1 virus infections reported by the World
Health Organization (WHO).
The initial
publication in the medical literature regarding this vaccine was 13 months ago
in the March 30, 2006 issue of the New England Journal of Medicine.
Director, Center for
Biologic Counterterrorism and Emerging Diseases
EROne Institutes,
Department of Emergency Medicine
Washington Hospital
Center, Washington, DC
Adjunct Professor of
Microbiology and immunology
Georgetown University
Medicine Center
e-mail: Daniel.r.Lucey@Medstar.net